Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Using suction in back-bleeding conditions increases cement penetration without the need for a tourniquet.

BACKGROUND: The majority of total knee arthroplasties are performed with a tourniquet as it is perceived this gives rise to superior cement fixation. Tourniquets, however, have been associated with increased pain, post-operative swelling, and reduced knee range of movement which can all detrimentally impact patient recovery. This laboratory-based study aimed to assess if it is possible to achieve equivalent (or even enhanced) cementation without a tourniquet using a novel suction device. METHODS: Cement penetration was compared between conditions simulating bone with back-bleeding with and without the use of suction in open-cell rigid foam tibia models and porcine specimens. Suction was applied via a urinary catheter inserted into the tibial recess created for the implant's stem. Cement penetration depth was measured from micro-CT scans. The pull-off strength of cemented tibial implant analogues in porcine specimens with and without suction was also assessed. RESULTS: Suction gave rise to a significant (p = 0.028) increase in cement penetration depth in both the rigid foam, 5.4 - 6.6 mm, and porcine specimens, 0.7 - 1.0 mm. A non-significant increase in implant pull-off strength was also observed. CONCLUSION: Suction during cementation in a back-bleeding model resulted in significantly greater cement penetration depth. Using suction surgeons can avoid potential disadvantages of tourniquet use without compromising cementation.

Medial/central PF arthritis and functionally stable ACL deficiency do not compromise outcomes of fixed-bearing medial UKA.

BACKGROUND: There is limited published data assessing functional scores and patient satisfaction following unicompartmental knee arthroplasty (UKA) in patients with patellofemoral (PF) arthritis or anterior cruciate ligament (ACL) deficiency. The purpose of this study was to determine whether medial/central PF arthritis or functionally stable ACL deficiency compromise outcomes of fixed-bearing medial UKA at a minimum follow-up of 2 years. The hypothesis was that equivalent outcomes can be achieved in patients with substantial medial/central PF arthritis or with functionally stable ACL deficiency. METHODS: The authors studied a consecutive series of 229 patients (240 knees) at 36.9 ± 6.3 months after receiving fixed-bearing medial UKA. Patients completed pre- and post-operative (2 years) clinical outcome questionnaires for Oxford Knee Score (OKS), EQ-5D, Knee injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS), University of California, Los Angeles (UCLA) activity score, and Forgotten Joint Score (FJS). Multivariable analyses were performed to determine associations between clinical scores, patient demographics, PF arthritis and functionally stable ACL deficiency. RESULTS: Of the 240 knees, 125 (54%) had substantial medial/central PF arthritis and 21 (9%) functionally stable ACL deficiency. Multivariable analyses revealed no association between outcomes and medial/central PF arthritis, but knees with functionally stable ACL deficiency were associated with better KOOS-PS (ß = 8.99, p = 0.012). CONCLUSION: Fixed-bearing medial UKA grants satisfactory outcomes at 2 years even in knees with substantial medial/central PF arthritis or functionally stable ACL deficiency. Longer-term prospective studies with larger cohorts are needed to confirm these promising findings regarding outcomes in patients traditionally contraindicated for medial UKA.

Pregravid weight is associated with prior dietary restraint and psychosocial factors during pregnancy.

The objective of this study was to investigate the association of pregravid weight status, previous dietary restraint, and psychosocial factors during pregnancy. We used data from the Pregnancy, Infection, and Nutrition study, which recruited 2,006 women at prenatal clinics before 20 weeks' gestation who were >16 years and English speaking. Institute of Medicine BMI cut points of underweight (<19.8), normal weight (19.8-26.0), overweight (>26.0-29.0), obese (>29.0-34.9), and an additional category extremely obese (> or =35.0), were used to categorize weight status. Eight psychosocial measures and dietary restraint were assessed with regard to BMI; perceived stress, trait anxiety, depressive symptoms, internal locus of control (LOC), chance LOC, powerful others LOC, self-esteem, and mastery. Linear regression was used to estimate associations, controlling for potential confounders. A significant trend was found between increasing pregravid weight categories and increasing scores for perceived stress, trait anxiety, depressive symptoms, powerful others LOC and dietary restraint, and decreasing scores for self-esteem and mastery. In adjusted models, pregravid obesity was independently associated with perceived stress, trait anxiety, and depressive symptoms. Extreme obesity was independently associated with all measures except internal LOC. A strong linear association was found between increasing weight categories and dietary restraint. In conclusion, as pregravid weight increased, pregnant women were at greater risk of reporting higher scores on negative psychosocial state and dietary restraints, and reporting lower score on positive personal dispositions.